NanoBio Corp

Translational Research: NanoBio Corporation

NanoBio® Corporation is a privately-held biopharmaceutical company focused on developing and commercializing novel products for the prevention and treatment of infectious diseases, based on its patented NanoStat™ technology platform. Founded in 2000 as a spin-out from the Center for Biologic Nanotechnology at the University of Michigan, NanoBio’s lead product candidates target treatments for herpes labialis (cold sores), onychomycosis (nail fungus), acne, cystic fibrosis and mucosal vaccines for influenza, pneumococcal and RSV. The company’s headquarters and laboratory facilities are located in Ann Arbor, Michigan and is staffed by 25 full time employees.

Nanoemulsion Applications for Therapeutics

The NanoStat™ platform technology enables both topical and mucosal anti-infective products. The technology employs high-energy, oil-in-water emulsions that are manufactured at a size of 150-400 nanometers and are stabilized by surfactants. When applied to the skin or mucous membranes, the nano-size nanoemulsion droplets rapidly penetrate through the epitelium via pores and hair shafts to the site of an infection. There, the droplets physically disrupt infectious agents by fusing with the outer membrane of the cell, killing the organism. The unique aspect of products derived from the company's NanoStat technology is that, unlike currently available therapies, NanoBio’s treatments are selectively toxic to microbes while non-irritating to skin and mucous membranes due to the sructure of human cells in tissue.

NanoStat™ based treatments have shown activity against bacteria (e.g., E. coli, Salmonella), viruses (e.g., HIV, Herpes), fungi (e.g., Candida albicans), and spores (e.g., Anthrax). This spectrum of activity allows for a broad range of anti-infective products. The company's anti-infective products pipeline includes candidates for the treatment of herpes labialis, genital herpes, onychomycosis, acne, Tinea capitis, Molluscum contagiousm, infections resultant from severe burns, methicillin resistant Staphylococcus aureus (MRSA). In addition, NanoBio has a product in development that could be an inhaled treatment for bacterial lung infections in cystic fibrosis patients. Success of this treatment in cystic fibrosis will also support using this material for lung infections in patients with COPD. Therapies for bladder and nasal infections are also envisioned.

The principal advantages of NanoStat therapies include:

Topically applied NanoStat therapeutics are not systemically absorbed but have proven efficacy equal or superior to systemic therapies;

NanoStat therapeutics have a broad spectrum of activity being effective against infections with bacteria, enveloped viruses, fungi, spores and protozoa;

Phase I and Phase II clinical trials of NanoStat therapeutics showed remarkable safety in in over 900 patients, proving that NanoStat drugs are non-irritating to the skin and mucous membranes;

NanoStat therapies have a broad therapeutic index as confirmed in multiple animal studies and in NanoBio’s clinical trials;

No cross resistance with antibiotics and a limited potential for drug resistance with NanoStat therapeutics, given the unique mechanism of action involving a physical process as opposed to inhibition of a chemical pathway.

The nanoemulsion is uniquely capable of permeating the nasal mucosa, where it loads vaccine antigen into immune-presenting cells. These cells then carry the antigen to areas of the body that initiate an immune response, including the lymph nodes, thymus and spleen producing both mucosal immunity and systemic immune response.

Mechanism of Action

Nasal delivery presents the antigen where it can most directly access the immune system

Induces robust mucosal immunity and a systemic Th1 cellular as well as a humoral response that protects against subsequent disease challenge

Cross protection

Adjuvants multiple antigen types

Non-inflammatory

Antigen-sparing

Thermally stable, requires no refrigeration

Needle-free, easy to administer

Inexpensive manufacturing

Clinical Trials Using NanoStat

The NanoStat technology has been proven in a number of large, well-controlled clinical trials. NanoBio has completed two, Phase 2 clinical trials in 814 subjects with recurrent herpes labialis, 567 of whom received NB-001 treatment for 4 or 10 days, or until lesion healing or the episode aborted. Using life table methods, there were statistically significant reductions in time to healing for 0.3% NB-001 versus vehicle of 1.2 and 1.3 days based upon the subject (p=0.012) and the investigator (p=0.006) assessments, respectively. This effect size is numerically larger (1.2 versus 0.5 days improvement) than the effect size seen with Abreva® and similar to that seen for the oral nucleoside analogues. The robust nature of these results was confirmed by re-analysis of the data for the subject assessment of time to healing dropping each center in turn from the analysis. All results were statistically significant with a range of p-values from 0.0012-0.0486.

NanoBio has completed a Phase 1 clinical trial in 20 patients and a Phase 2 clinical trial in 463 patients with onychomycosis. In the latter trial, 331 patients received NB-002 treatment for up to 42 weeks. Robust antifungal effects were demonstrated in all treated groups versus the control group and significant clinical responses were observed in patients with mild disease.

An ongoing study is examining the ability of NB-00X to reduce P. acnes bacterial counts in healthy adult volunteers. A total of 140 subjects received nanoemulsion-adjuvanted Fluzone® vaccine intranasally. The results of HAI titer determinations significant adjuvant activity that would allow licensure based on serum titers. In addition, there were no treatment related withdrawals and no serious adverse events. These results are unique for a nasal vaccine.

Funding

To date, over $110 million has been invested in the company's NanoStat™ technology platform through research grants and equity investments, including $45 million in private equity financing from Perseus, LLC. These investments have enabled extensive studies supporting the expansion of the company’s dermatology, anti-infective and mucosal vaccine programs.

Jobs

Since 2007 NanoBio has nearly tripled in size to 28 employees and has subcontracted numerous clinical and preclinical projects to Michigan based life sciences companies.

Collaborations

The National Institute of Allergy and Infectious Diseases, a Division of The National Institute of Health, named NanoBio as a subcontractor in a joint award with the University of Michigan for a project titled, “Innate Immune Receptors and Adjuvant Discovery”. NanoBio will receive approximately $4.1M of the total $9.3M awarded over a five-year period to support research efforts aimed at developing nanoemulsion-based mucosal vaccine adjuvants for a wide variety of antigens.

A second interaction relates to a recently awarded $7M contract from the Gates’ Foundation to NanoBio to develop an RSV vaccine. UM will receive approximately $2M of the total awarded over a two-year period to support research efforts aimed at nanoemulsion-based mucosal vaccine adjuvants for RSV.

GlaxoSmithKline (GSK): NanoBio Corporation and GSK announced an exclusive licensing agreement in the United States and Canada for the over-the-counter (OTC) use of NB-001, a novel, patented compound representing the next advance in the treatment of cold sores. Developed by NanoBio, NB-001 provides significant antimicrobial activity against the virus that causes cold sores, herpes labialis. Cold sores are a prevalent condition affecting approximately 20% of the adult population in the US.

This agreement with GSK provided NanoBio with an upfront payment of $14.5 million and is eligible to receive additional milestone payments of up to $40 million plus single digit royalties on future sales.

Several other collaborations are pending to include a significant partnering agreement with a global pharmaceutical company. Other collaborations with the University include preclinical research for treatments for wounds and burns, cystic fibrosis and several vaccine candidates.